Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001219045 | SCV001390965 | uncertain significance | Familial cancer of breast; Fanconi anemia complementation group J | 2019-08-18 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRIP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 526 of the BRIP1 protein (p.Met526Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. |
KCCC/NGS Laboratory, |
RCV003346381 | SCV004046893 | uncertain significance | Familial cancer of breast | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 526 of the BRIP1 protein (p.Met526Ile). The methionine residue is weakly conserved (PhyloP=2.2) and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (gnomAD). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. In silico predictions show benign predictions . In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |